Dupilumab-associated head and neck dermatitis: Rapid response with abrocitinib treatment.

Development or exacerbation of head and neck dermatitis (HN-D) in association with dupilumab has been reported. Severity of HN-D varies, and may persist even with discontinuation of dupilumab. Development or exacerbation of HN-D is not yet completely understood, and various hypotheses have been made about the possible underlying pathophysiology. To date, there is no established treatment for HN-D in association with dupilumab. We report 2 cases of HN-D occurring following dupilumab treatment, with significant improvement of HN-D following treatment with abrocitinib.

Impact of Atopic Dermatitis on Quality of Life of Caregivers: A Systematic Review and Meta-Analysis.

Abstracts: Background: Atopic dermatitis (AD) is a chronic dermatological condition that affects both patients and their caregivers. Aims: To summarize evidence on the impact of AD on the quality of life (QoL) of caregiver. Methods: Observational studies were searched for in Medline, Embase, Cochrane Library, SCOPUS, and CINAHL databases up till March 1, 2023. Results: Seventy studies with a total of 33,291 study participants were identified. The Dermatitis Family Index (DFI) questionnaire featured in 29 studies and was chosen for further meta-analysis. The pooled DFI for all studies was 9.35 (95% confidence interval [CI] 6.94-11.76). For individual components, the highest component scores were for 1.24 for expenditure (95% CI 0.80-1.69), followed by 1.14 for emotions (95% CI 0.77-1.50), as well as sleep 1.12 (95% CI 0.71-1.54) and exhaustion 1.12 (95% CI 0.76-1.48). Meta-analysis on the effect of patient QoL on family QoL was conducted on 15 studies, with a pooled Spearman's rank coefficient using Infants' Dermatitis Quality of Life Index (IDQoL) was 0.632 (95% CI 0.558-0.707), whereas that using Children's Dermatology Life Quality Index (CDLQI) was 0.624 (95% CI 0.507-0.741). For the 17 studies correlating AD severity with family QoL, a pooled Spearman's rank coefficient of 0.425 (95% CI 0.330-0.521) was obtained. Conclusions: AD is associated with significant negative impacts on caregiver QoL, particularly in family finance, caregiver burnout, and sleep impairment. This was consistently affected by AD severity and patient QoL in all studies examining this association.

Efficacy and safety of narrowband ultraviolet B versus combined ultraviolet A/narrowband ultraviolet B phototherapy in the treatment of chronic atopic dermatitis: A randomised double-blind study.

Phototherapy is a useful treatment modality for atopic dermatitis (AD). This is a prospective randomised double-blind study comparing the clinical efficacy of combined ultraviolet-A (UVA)/narrowband ultraviolet-B (NBUVB) versus NBUVB phototherapy in the treatment of chronic AD. Patients with moderate-to-severe AD were randomised to receive either UVA/NBUVB or NBUVB phototherapy twice weekly over 12 weeks. At baseline, weeks 6 and 12, Eczema Area And Severity Index (EASI), itch score and adverse effects were assessed. At baseline and week 12, disease-related quality of life was evaluated using the Dermatology Life Quality Index (DLQI). Nine patients were randomised to receive UVA/NBUVB and 10 received NBUVB. At week 12, both groups showed significant improvement in EASI and itch scores (p < 0.05). Significant improvement in DLQI was seen in the UVA/NBUVB arm (p = 0.009) with a trend towards improvement in the NBUVB arm (p = 0.11). The efficacy of both modalities were comparable, as were reported adverse effects aside from skin dryness which was higher in the NBUVB arm (40% vs. 0%, p = 0.033). Combined UVA/NBUVB and NBUVB phototherapy have comparable clinical efficacy and safety in the treatment of chronic AD. NBUVB may induce greater skin dryness.

Safety and efficacy of dupilumab in adult atopic dermatitis in Singapore.

INTRODUCTION: Dupilumab, a biologic approved for treatment of moderate-to-severe atopic dermatitis (AD), has been reported to be largely effective with minimal adverse effects. However, being a targeted therapy, its effectiveness and side effects are expected to be varied in a heterogeneous ethnic population. Currently, the majority of studies on dupilumab are based on Western populations. METHODS: A retrospective cohort of 51 patients with moderate-to-severe AD treated with dupilumab at a tertiary skin institute from January 2018 to February 2020 was included. Outcome measures such as Scoring Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI) and Dermatology Quality of Life Index (DLQI) were analysed at baseline and after 16 weeks of treatment. Laboratory tests at the respective time points were also measured. RESULTS: Patients treated with dupilumab showed consistent reduction in body surface area (BSA) involved, SCORAD, EASI and DLQI scores. Concurrently, serum immunoglobulin E (IgE) and absolute eosinophil count showed a downward trend at 4 months of treatment. There was a transient increase in mean serum IgE at 1 month of dupilumab treatment. Also, 42.0% and 35.3% of patients developed eye symptoms, and head and neck dermatitis, respectively, but there were no major adverse events reported. Childhood-onset AD was more likely to have improved BSA scores compared to adult-onset AD. CONCLUSIONS: Our study confirms the efficacy of dupilumab with real-world data in an adult Asian population. Higher proportions of eye symptoms, and head and neck dermatitis were observed in our cohort compared to other Asian clinical cohort studies. Further studies are needed to evaluate these differences.

A Malassezia pseudoprotease dominates the secreted hydrolase landscape and is a potential allergen on skin.

Malassezia globosa is abundant and prevalent on sebaceous areas of the human skin. Genome annotation reveals that M. globosa possesses a repertoire of secreted hydrolytic enzymes relevant for lipid and protein metabolism. However, the functional significance of these enzymes is uncertain and presence of these genes in the genome does not always translate to expression at the cutaneous surface. In this study we utilized targeted RNA sequencing from samples isolated directly from the skin to quantify gene expression of M. globosa secreted proteases, lipases, phospholipases and sphingomyelinases. Our findings indicate that the expression of these enzymes is dynamically regulated by the environment in which the fungus resides, as different growth phases of the planktonic culture of M. globosa show distinct expression levels. Furthermore, we observed significant differences in the expression of these enzymes in culture compared to healthy sebaceous skin sites. By examining the in situ gene expression of M. globosa's secreted hydrolases, we identified a predicted aspartyl protease, MGL_3331, which is highly expressed on both healthy and disease-affected dermatological sites. However, molecular modeling and biochemical studies revealed that this protein has a non-canonical active site motif and lacks measurable proteolytic activity. This pseudoprotease MGL_3331 elicits a heightened IgE-reactivity in blood plasma isolated from patients with atopic dermatitis compared to healthy individuals and invokes a pro-inflammatory response in peripheral blood mononuclear cells. Overall, our study highlights the importance of studying fungal proteins expressed in physiologically relevant environments and underscores the notion that secreted inactive enzymes may have important functions in influencing host immunity.

Atopic dermatitis: A global health perspective.

The International Society of AD (ISAD) organized a roundtable on global aspects of AD at the WCD 2023 in Singapore. According to the Global Burden of Disease (GBD) consortium, at least 171 million individuals were affected with AD in 2019, corresponding to 2.23% of the world population, with age-standardized prevalence and incidence rates that were relatively stable from 1990 to 2019. Based on the panel experience, most AD cases are mild-to-moderate. Without parallel data on disease prevalence and severity, the GBD data are difficult to interpret in many regions. This gap is particularly important in countries with limited medical infrastructure, but indirect evidence suggests a significant burden of AD in low-and-medium resource settings, especially urban areas. The Singapore roundtable was an opportunity to compare experiences in World Bank category 1 (Madagascar and Mali), 3 (Brazil, China) and 4 (Australia, Germany, Qatar, USA, Singapore, Japan) countries. The panel concluded that current AD guidelines are not adapted for low resource settings and a more pragmatic approach, as developed by WHO for skin NTDs, would be advisable for minimal access to moisturizers and topical corticosteroids. The panel also recommended prioritizing prevention studies, regardless of the level of existing resources. For disease long-term control in World Bank category 3 and most category 4 countries, the main problem is not access to drugs for most mild-to-moderate cases, but rather poor compliance due to insufficient time at visits. Collaboration with WHO, patient advocacy groups and industry may promote global change, improve capacity training and fight current inequalities. Finally, optimizing management of AD and its comorbidities needs more action at the primary care level, because reaching specialist care is merely aspirational in most settings. Primary care empowerment with store and forward telemedicine and algorithms based on augmented intelligence is a future goal.

Non-invasive biochemical analysis and comparison of atopic dermatitis and psoriasis skin using handheld confocal Raman spectroscopy.

A handheld non-invasive confocal Raman system (CRS) was used to evaluate the differences in skin biochemicals between atopic dermatitis (AD) and psoriasis, which are inflammatory skin conditions. Raman spectral measurements in the fingerprint and high wavenumber region were acquired using a portable in-house CRS system with excitation lasers operating at 671 and 785 nm. It was deduced that relative amount of water decreases in the following sequence of skin: healthy, psoriasis and AD. Moreover, differential trends were observed for the subclasses of ceramides such that ceramide 3 is lower in the lesional AD and psoriasis skin as compared to healthy, while ceramide 2 showed a contrasting trend of decrease in lesional AD and increase in lesional psoriasis as opposed to healthy skin. Amount of cholesterol was significantly higher in lesional psoriasis as compared to lesional AD and healthy skin. These differences can aid in an objective classification of the skin conditions and in the formulation of new disease-specific topical treatments.

Understanding Discordant Perceptions of Disease Severity Between Physicians and Patients With Eczema and Psoriasis Using Structural Equation Modeling.

Importance: Patients and physicians often have differing opinions on the patient's disease severity. This phenomenon, termed discordant severity grading (DSG), hinders the patient-physician relationship and is a source of frustration. Objective: To test and validate a model explaining the cognitive, behavioral, and disease factors associated with DSG. Design, Setting, and Participants: A qualitative study was first performed to derive a theoretical model. In this subsequent prospective cross-sectional quantitative study, the qualitatively derived theoretical model was validated using structural equation modeling (SEM). Recruitment was conducted between October 2021 and September 2022. This was a multicenter study in 3 Singapore outpatient tertiary dermatological centers. Dermatology patients and their attending physicians were recruited by convenience sampling. Patients were aged 18 to 99 years with psoriasis or eczema of at least 3 months' duration and recruited only once. The data were analyzed between October 2022 to May 2023. Main Outcomes and Measures: The outcome was the difference between global disease severity (0-10 numerical rating scale with a higher score indicating greater severity) as independently scored by the patient and the dermatologist. Positive discordance was defined as patient-graded severity more than 2 points higher (graded more severely) than physicians, and negative discordance if more than 2 points lower than physicians. Confirmatory factor analysis followed by SEM was used to assess the associations between preidentified patient, physician, and disease factors with the difference in severity grading. Results: Of the 1053 patients (mean [SD] age, 43.5 [17.5] years), a total of 579 (55.0%) patients were male, 802 (76.2%) had eczema, and 251 (23.8%) had psoriasis. Of 44 physicians recruited, 20 (45.5%) were male, 24 (54.5%) were aged between 31 and 40 years, 20 were senior residents or fellows, and 14 were consultants or attending physicians. The median (IQR) number of patients recruited per physician was 5 (2-18) patients. Of 1053 patient-physician pairs, 487 pairs (46.3%) demonstrated discordance (positive, 447 [42.4%]; negative, 40 [3.8%]). Agreement between patient and physician rating was poor (intraclass correlation, 0.27). The SEM analyses showed that positive discordance was associated with higher symptom expression (standardized coefficient B = 0.12; P = .02) and greater quality-of-life impairment (B = 0.31; P < .001), but not patient or physician demographics. A higher quality-of-life impairment was in turn associated with lower resilience and stability (B = -0.23; P < .001), increased negative social comparisons (B = 0.45; P < .001), lower self-efficacy (B = -0.11; P = .02), increased disease cyclicity (B = 0.47; P < .001), and greater expectation of chronicity (B = 0.18; P < .001). The model was well-fitted (Tucker-Lewis: 0.94; Root Mean Square Error of Approximation: 0.034). Conclusions and Relevance: This cross-sectional study identified various modifiable contributory factors to DSG, increased understanding of the phenomenon, and set a framework for targeted interventions to bridge this discordance.

Investigating causal relationships between obesity and skin barrier function in a multi-ethnic Asian general population cohort.

BACKGROUND: Skin diseases impact significantly on the quality of life and psychology of patients. Obesity has been observed as a risk factor for skin diseases. Skin epidermal barrier dysfunctions are typical manifestations across several dermatological disturbances. OBJECTIVES: We aim to establish the association between obesity and skin physiology measurements and investigate whether obesity may play a possible causal role on skin barrier dysfunction. METHODS: We investigated the relationship of obesity with skin physiology measurements, namely transepidermal water loss (TEWL), skin surface moisture and skin pH in an Asian population cohort (n = 9990). To assess for a possible causal association between body mass index (BMI) and skin physiology measurements, we performed Mendelian Randomization (MR), along with subsequent additional analyses to assess the potential causal impact of known socioeconomic and comorbidities of obesity on TEWL. RESULTS: Every 1 kg/m2 increase in BMI was associated with a 0.221% (95%CI: 0.144-0.298) increase in TEWL (P = 2.82E-08), a 0.336% (95%CI: 0.148-0.524) decrease in skin moisture (P = 4.66E-04) and a 0.184% (95%CI: 0.144-0.224) decrease in pH (P = 1.36E-19), adjusting for age, gender, and ethnicity. Relationships for both TEWL and pH with BMI remained strong (Beta 0.354; 95%CI: 0.189-0.520 and Beta -0.170; 95%CI: -0.253 to -0.087, respectively) even after adjusting for known confounders, with MR experiments further supporting BMI's possible causal relationship with TEWL. Based on additional MR performed, none of the socioeconomic and comorbidities of obesity investigated are likely to have possible causal relationships with TEWL. CONCLUSION: We establish strong association of BMI with TEWL and skin pH, with MR results suggestive of a possible causal relationship of obesity with TEWL. It emphasizes the potential impact of obesity on skin barrier function and therefore opportunity for primary prevention.

Evaluating and comparing the clinical characteristics between adult-onset and childhood-onset atopic dermatitis in an Asian clinical cohort.

BACKGROUND: Atopic dermatitis (AD) is one of the most prevalent chronic inflammatory skin conditions. We aimed to describe the clinical features of adult-onset and childhood-onset AD in a multi-ethnic Asian population. METHODS: A retrospective study was performed of 188 patients with AD managed at a tertiary skin institution in Singapore. Patient demographics, clinical features and disease scores were analysed. RESULTS: Clinical features related to pigmentary changes, such as orbital darkening and Dennie-Morgan folds were more prevalent among childhood-onset AD patients than in adult-onset AD patients. Similarly, features related to prolonged scratching or friction, such as anterior neck folds, perifollicular accentuation and infra-auricular/infranasal fissuring were also more prevalent in childhood-onset AD patients. Disease scores such as SCORAD and EASI were not different between patients with childhood versus adult-onset disease. CONCLUSION: There were significant differences in clinical features between childhood-onset and adult-onset AD. Certain features are related to pigmentary changes and might be more accentuated in patients with skin of colour. Further studies are needed to understand how the different features might be clinically significant and related to the various AD endotypes and disease trajectories.

Epidemiology of adult patients with atopic dermatitis in AWARE 1: A second international survey.

Background: There are gaps in our understanding of the epidemiology of atopic dermatitis (AD) in adults. Objective: To evaluate the prevalence and severity of AD in adults from countries/regions within Asia, Eurasia, Latin America, Middle East, and Russia. Methods: This international, web-based survey was performed in Argentina, Brazil, China, Colombia, Egypt, Hong Kong, Israel, Malaysia, Mexico, Russia, Kingdom of Saudi Arabia (KSA), Singapore, Taiwan, Thailand, Turkey, and United Arab Emirates. Questionnaires were sent to adult members of online respondent panels for determination of AD and assessment of severity. A diagnosis of AD required respondents to meet the modified United Kingdom (UK) Working Party criteria and to self-report they had a physician diagnosis of AD. Severity of AD was determined using Patient-Oriented Scoring of Atopic Dermatitis (PO-SCORAD), Patient-Oriented Eczema Measure (POEM), and Patient Global Assessment (PGA). Results: Among respondents by country/region the prevalence of AD ranged from 3.4% in Israel to 33.7% in Thailand. The prevalence was generally higher in females versus males. Severity varied by scale, although regardless of scale the proportion of respondents with mild and moderate disease was higher than severe disease. PGA consistently resulted in the lowest proportion of severe AD (range 2.4% China - 10.8% Turkey) relative to PO-SCORAD (range 13.4% China - 41.6% KSA) and POEM (range 5.1% China - 16.6% Israel). Conclusions: This survey highlights the importance of AD in adults, with high prevalence and high morbidity among respondents and emphasizes that AD is not just a disease of childhood-there is disease persistence and chronicity in adults.

Adiposity impacts cognitive function in Asian populations: an epidemiological and Mendelian Randomization study.

Background: Obesity and related metabolic disturbances including diabetes, hypertension and hyperlipidemia predict future cognitive decline. Asia has a high prevalence of both obesity and metabolic disease, potentially amplifying the future burden of dementia in the region. We aimed to investigate the impact of adiposity and metabolic risk on cognitive function in Asian populations, using an epidemiological analysis and a two-sample Mendelian Randomization (MR) study. Methods: The Health for Life in Singapore (HELIOS) Study is a population-based cohort of South-East-Asian men and women in Singapore, aged 30-84 years. We analyzed 8769 participants with metabolic and cognitive data collected between 2018 and 2021. Whole-body fat mass was quantified with Dual X-Ray Absorptiometry (DEXA). Cognition was assessed using a computerized cognitive battery. An index of general cognition ' g ' was derived through factor analysis. We tested the relationship of fat mass indices and metabolic measures with ' g ' using regression approaches. We then performed inverse-variance-weighted MR of adiposity and metabolic risk factors on ' g ', using summary statistics for genome-wide association studies of BMI, visceral adipose tissue (VAT), waist-hip-ratio (WHR), blood pressure, HDL cholesterol, triglycerides, fasting glucose, HbA1c, and general cognition. Findings: Participants were 58.9% female, and aged 51.4 (11.3) years. In univariate analysis, all 29 adiposity and metabolic measures assessed were associated with ' g ' at P < 0.05. In multivariable analyses, reduced ' g ' was consistently associated with increased visceral fat mass index and lower HDL cholesterol (P < 0.001), but not with blood pressure, triglycerides, or glycemic indices. The reduction in ' g ' associated with 1SD higher visceral fat, or 1SD lower HDL cholesterol, was equivalent to a 0.7 and 0.9-year increase in chronological age respectively (P < 0.001). Inverse variance MR analyses showed that reduced ' g ' is associated with genetically determined elevation of VAT, BMI and WHR (all P < 0.001). In contrast, MR did not support a causal role for blood pressure, lipid, or glycemic indices on cognition. Interpretation: We show an independent relationship between adiposity and cognition in a multi-ethnic Asian population. MR analyses suggest that both visceral adiposity and raised BMI are likely to be causally linked to cognition. Our findings have important implications for preservation of cognitive health, including further motivation for action to reverse the rising burden of obesity in the Asia-Pacific region. Funding: The Nanyang Technological University-the Lee Kong Chian School of Medicine, National Healthcare Group, National Medical Research Council, Ministry of Education, Singapore.

Incidence of skin malignancies in patients with vitiligo or psoriasis who received narrowband ultraviolet B phototherapy (308 nm/311 nm): A retrospective review of 3730 patients.

BACKGROUND: Previous studies regarding the risk of skin malignancy with NBUVB have been performed in Caucasian patients, but few studies have been conducted in Asians. AIM: The aim of the study was to determine the risk of skin cancer in Asian patients with psoriasis and vitiligo receiving NBUVB phototherapy. METHODS: We performed a 9-year retrospective study including all patients with psoriasis and vitiligo receiving NBUVB (either 311 nm wavelength through cabin phototherapy or 308 nm through excimer lamp phototherapy) at the National Skin Centre. We matched the identification numbers of patients to the National Registry of Diseases Office database and collected data on all skin cancers diagnosed. RESULTS: A total of 3730 patients were included. During the course of the study, 12 cases of skin cancer were diagnosed, of which 10 were basal cell carcinomas, and 2 were squamous cell carcinomas. No cases of melanoma were detected in the study. The age-standardized incidence of skin cancer in psoriasis and vitiligo patients who received phototherapy was 47.5 and 26.5, respectively, which is higher than the incidence of skin cancers in the general population. Risk of skin malignancy was positively correlated with the cumulative (p = .008) and maximum dose of phototherapy (p = .011) as well as previous systemic treatments (p = .006). LIMITATIONS: Limitations include a relatively short follow-up period as well as the lack of quantification of solar exposure. CONCLUSIONS: NBUVB phototherapy in Asian skin increases the risk of skin malignancy. The risk of skin malignancy is higher with psoriasis patients, greater cumulative and maximal dose of phototherapy as well as the use of systemic therapy. Despite the increased risk, the absolute number of skin malignancies remains low, especially for vitiligo patients, with no cases of melanoma diagnosed-a reassuring finding that phototherapy remains a safe alternative in the treatment of psoriasis and vitiligo.

Multispectral raster-scanning optoacoustic mesoscopy differentiate lesional from non-lesional atopic dermatitis skin using structural and functional imaging markers.

Atopic dermatitis (AD) is a chronic and pruritic skin inflammatory disease causing a significant burden to health care management and patient's quality of life. Seemingly healthy skin or non-lesional sites on AD patients still presents skin barrier defects and immune response, which can develop to AD at a later stage. To investigate further the balance between the epidermal barrier impairment and intrinsic immune dysregulation in AD, we exploited multispectral Raster-Scanning Optoacoustic Mesoscopy (ms-RSOM) to image lesional and non-lesional skin areas on AD patients of different severities non-invasively to elucidate their structural features and functional information. Herein, we demonstrate the objective assessment of AD severity using relative changes in oxygen saturation (δsO2) levels in microvasculature along with other structural parameters such as relative changes in epidermis thickness (δET) and total blood volume (δTBV) between the lesional and non-lesional areas of the skin. We could observe an increasing trend for δsO2 and δTBV, which correlated well with the subjective clinical Scoring Atopic Dermatitis (SCORAD) for evaluating the severity. Notably, δET showed a decreasing trend with AD severity, indicating that the difference in epidermal thickness between lesional and non-lesional area of the skin decreases with AD severity. Our results also correlated well with conventional metrics such as trans-epidermal water loss (TEWL) and erythrosine sedimentation rate (ESR). We quantified the δsO2 and δET changes to objectively evaluate the treatment response before and four months after treatment using topical steroids and cyclosporine in one severe AD patient. We observed reduced δsO2 and δET post treatment. We envision that in future, functional and structural imaging metrics derived from ms-RSOM can be translated as objective markers to assess and stratify the severity of AD and understand the function of skin barrier dysfunctions and immune dysregulation. It could also be employed to monitor the treatment response of AD in regular clinical settings.